4rer - Revision history

OCA at 17:49, 20 September 2023

2023-09-20T17:49:03Z

← Older revision		Revision as of 17:49, 20 September 2023
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	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4rer]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4RER OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4RER FirstGlance]. <br>		<table><tr><td colspan='2'>[[4rer]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4RER OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4RER FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=AMP:ADENOSINE+MONOPHOSPHATE'>AMP</scene>, <scene name='pdbligand=EPE:4-(2-HYDROXYETHYL)-1-PIPERAZINE+ETHANESULFONIC+ACID'>EPE</scene>, <scene name='pdbligand=GLC:ALPHA-D-GLUCOSE'>GLC</scene>, <scene name='pdbligand=PRD_900012:beta-cyclodextrin'>PRD_900012</scene>, <scene name='pdbligand=SEP:PHOSPHOSERINE'>SEP</scene>, <scene name='pdbligand=STU:STAUROSPORINE'>STU</scene>, <scene name='pdbligand=TPO:PHOSPHOTHREONINE'>TPO</scene></td></tr>		</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models\|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution\|Resolution]] 4.047Å</td></tr>
			<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=AMP:ADENOSINE+MONOPHOSPHATE'>AMP</scene>, <scene name='pdbligand=EPE:4-(2-HYDROXYETHYL)-1-PIPERAZINE+ETHANESULFONIC+ACID'>EPE</scene>, <scene name='pdbligand=GLC:ALPHA-D-GLUCOSE'>GLC</scene>, <scene name='pdbligand=PRD_900012:beta-cyclodextrin'>PRD_900012</scene>, <scene name='pdbligand=SEP:PHOSPHOSERINE'>SEP</scene>, <scene name='pdbligand=STU:STAUROSPORINE'>STU</scene>, <scene name='pdbligand=TPO:PHOSPHOTHREONINE'>TPO</scene></td></tr>
	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4rer FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4rer OCA], [https://pdbe.org/4rer PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4rer RCSB], [https://www.ebi.ac.uk/pdbsum/4rer PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4rer ProSAT]</span></td></tr>		<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4rer FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4rer OCA], [https://pdbe.org/4rer PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4rer RCSB], [https://www.ebi.ac.uk/pdbsum/4rer PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4rer ProSAT]</span></td></tr>
	</table>		</table>

OCA at 06:52, 2 March 2023

2023-03-02T06:52:59Z

← Older revision		Revision as of 06:52, 2 March 2023
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	<StructureSection load='4rer' size='340' side='right'caption='[[4rer]], [[Resolution\|resolution]] 4.05Å' scene=''>		<StructureSection load='4rer' size='340' side='right'caption='[[4rer]], [[Resolution\|resolution]] 4.05Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4rer]] is a 3 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/~~Human Human~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4RER OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=4RER FirstGlance]. <br>		<table><tr><td colspan='2'>[[4rer]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4RER OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4RER FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=AMP:ADENOSINE+MONOPHOSPHATE'>AMP~~</scene>, <scene name='pdbligand=BCD:BETA-CYCLODEXTRIN'>BCD~~</scene>, <scene name='pdbligand=EPE:4-(2-HYDROXYETHYL)-1-PIPERAZINE+ETHANESULFONIC+ACID'>EPE</scene>, <scene name='pdbligand=~~STU~~:~~STAUROSPORINE~~'>~~STU~~</scene><~~/td></tr>~~		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=AMP:ADENOSINE+MONOPHOSPHATE'>AMP</scene>, <scene name='pdbligand=EPE:4-(2-HYDROXYETHYL)-1-PIPERAZINE+ETHANESULFONIC+ACID'>EPE</scene>, <scene name='pdbligand=GLC:ALPHA-D-GLUCOSE'>GLC</scene>, <scene name='pdbligand=PRD_900012:beta-cyclodextrin'>PRD_900012</scene>, <scene name='pdbligand=SEP:PHOSPHOSERINE'>SEP</scene>, <scene name='pdbligand=STU:STAUROSPORINE'>STU</scene>, <scene name='pdbligand=TPO:PHOSPHOTHREONINE'>TPO</scene></td></tr>
	~~<tr id~~='~~NonStdRes'><td class~~=~~"sblockLbl"><b>[[Non~~-~~Standard_Residue\|NonStd Res:]]</b~~></~~td><td class="sblockDat"~~><scene name='pdbligand=SEP:PHOSPHOSERINE'>SEP</scene>, <scene name='pdbligand=~~TPO~~:~~PHOSPHOTHREONINE~~'>~~TPO~~</scene><~~/td></tr>~~		<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4rer FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4rer OCA], [https://pdbe.org/4rer PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4rer RCSB], [https://www.ebi.ac.uk/pdbsum/4rer PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4rer ProSAT]</span></td></tr>
	~~<tr id~~='~~related'><td class~~=~~"sblockLbl"><b>[[Related_structure\|Related~~:~~]]</b></td><td class="sblockDat">[[4red\|4red]], [[4rew\|4rew]]</td></tr>~~
	~~<tr id='gene~~'>~~<td class="sblockLbl"><b>[[Gene\|Gene:]]~~</~~b></td><td class="sblockDat"~~>AMPK1, Human holo-AMPK alpha1 subunit, PRKAA1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), Human holo-AMPK beta2 subunit, PRKAB2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), Human holo-AMPK gamma1 subunit, PRKAG1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=4rer FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4rer OCA], [~~http~~://pdbe.org/4rer PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=4rer RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/4rer PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=4rer ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
	[~~[http~~://www.uniprot.org/uniprot/AAPK1_HUMAN AAPK1_HUMAN]] Catalytic subunit of AMP-activated protein kinase (AMPK), an energy sensor protein kinase that plays a key role in regulating cellular energy metabolism. In response to reduction of intracellular ATP levels, AMPK activates energy-producing pathways and inhibits energy-consuming processes: inhibits protein, carbohydrate and lipid biosynthesis, as well as cell growth and proliferation. AMPK acts via direct phosphorylation of metabolic enzymes, and by longer-term effects via phosphorylation of transcription regulators. Also acts as a regulator of cellular polarity by remodeling the actin cytoskeleton; probably by indirectly activating myosin. Regulates lipid synthesis by phosphorylating and inactivating lipid metabolic enzymes such as ACACA, ACACB, GYS1, HMGCR and LIPE; regulates fatty acid and cholesterol synthesis by phosphorylating acetyl-CoA carboxylase (ACACA and ACACB) and hormone-sensitive lipase (LIPE) enzymes, respectively. Regulates insulin-signaling and glycolysis by phosphorylating IRS1, PFKFB2 and PFKFB3. AMPK stimulates glucose uptake in muscle by increasing the translocation of the glucose transporter SLC2A4/GLUT4 to the plasma membrane, possibly by mediating phosphorylation of TBC1D4/AS160. Regulates transcription and chromatin structure by phosphorylating transcription regulators involved in energy metabolism such as CRTC2/TORC2, FOXO3, histone H2B, HDAC5, MEF2C, MLXIPL/ChREBP, EP300, HNF4A, p53/TP53, SREBF1, SREBF2 and PPARGC1A. Acts as a key regulator of glucose homeostasis in liver by phosphorylating CRTC2/TORC2, leading to CRTC2/TORC2 sequestration in the cytoplasm. In response to stress, phosphorylates 'Ser-36' of histone H2B (H2BS36ph), leading to promote transcription. Acts as a key regulator of cell growth and proliferation by phosphorylating TSC2, RPTOR and ATG1/ULK1: in response to nutrient limitation, negatively regulates the mTORC1 complex by phosphorylating RPTOR component of the mTORC1 complex and by phosphorylating and activating TSC2. In response to nutrient limitation, promotes autophagy by phosphorylating and activating ATG1/ULK1. AMPK also acts as a regulator of circadian rhythm by mediating phosphorylation of CRY1, leading to destabilize it. May regulate the Wnt signaling pathway by phosphorylating CTNNB1, leading to stabilize it. Also has tau-protein kinase activity: in response to amyloid beta A4 protein (APP) exposure, activated by CAMKK2, leading to phosphorylation of MAPT/TAU; however the relevance of such data remains unclear in vivo. Also phosphorylates CFTR, EEF2K, KLC1, NOS3 and SLC12A1.<ref>PMID:11518699</ref> <ref>PMID:11554766</ref> <ref>PMID:12519745</ref> <ref>PMID:14651849</ref> <ref>PMID:15866171</ref> <ref>PMID:17486097</ref> <ref>PMID:17711846</ref> <ref>PMID:18184930</ref> <ref>PMID:18439900</ref> <ref>PMID:20074060</ref> <ref>PMID:20160076</ref> <ref>PMID:21205641</ref> [[http://www.uniprot.org/uniprot/AAKG1_HUMAN AAKG1_HUMAN]] AMP/ATP-binding subunit of AMP-activated protein kinase (AMPK), an energy sensor protein kinase that plays a key role in regulating cellular energy metabolism. In response to reduction of intracellular ATP levels, AMPK activates energy-producing pathways and inhibits energy-consuming processes: inhibits protein, carbohydrate and lipid biosynthesis, as well as cell growth and proliferation. AMPK acts via direct phosphorylation of metabolic enzymes, and by longer-term effects via phosphorylation of transcription regulators. Also acts as a regulator of cellular polarity by remodeling the actin cytoskeleton; probably by indirectly activating myosin. Gamma non-catalytic subunit mediates binding to AMP, ADP and ATP, leading to activate or inhibit AMPK: AMP-binding results in allosteric activation of alpha catalytic subunit (PRKAA1 or PRKAA2) both by inducing phosphorylation and preventing dephosphorylation of catalytic subunits. ADP also stimulates phosphorylation, without stimulating already phosphorylated catalytic subunit. ATP promotes dephosphorylation of catalytic subunit, rendering the AMPK enzyme inactive.<ref>PMID:21680840</ref> [[http://www.uniprot.org/uniprot/AAKB2_HUMAN AAKB2_HUMAN]] Non-catalytic subunit of AMP-activated protein kinase (AMPK), an energy sensor protein kinase that plays a key role in regulating cellular energy metabolism. In response to reduction of intracellular ATP levels, AMPK activates energy-producing pathways and inhibits energy-consuming processes: inhibits protein, carbohydrate and lipid biosynthesis, as well as cell growth and proliferation. AMPK acts via direct phosphorylation of metabolic enzymes, and by longer-term effects via phosphorylation of transcription regulators. Also acts as a regulator of cellular polarity by remodeling the actin cytoskeleton; probably by indirectly activating myosin. Beta non-catalytic subunit acts as a scaffold on which the AMPK complex assembles, via its C-terminus that bridges alpha (PRKAA1 or PRKAA2) and gamma subunits (PRKAG1, PRKAG2 or PRKAG3).		[https://www.uniprot.org/uniprot/AAPK1_HUMAN AAPK1_HUMAN] Catalytic subunit of AMP-activated protein kinase (AMPK), an energy sensor protein kinase that plays a key role in regulating cellular energy metabolism. In response to reduction of intracellular ATP levels, AMPK activates energy-producing pathways and inhibits energy-consuming processes: inhibits protein, carbohydrate and lipid biosynthesis, as well as cell growth and proliferation. AMPK acts via direct phosphorylation of metabolic enzymes, and by longer-term effects via phosphorylation of transcription regulators. Also acts as a regulator of cellular polarity by remodeling the actin cytoskeleton; probably by indirectly activating myosin. Regulates lipid synthesis by phosphorylating and inactivating lipid metabolic enzymes such as ACACA, ACACB, GYS1, HMGCR and LIPE; regulates fatty acid and cholesterol synthesis by phosphorylating acetyl-CoA carboxylase (ACACA and ACACB) and hormone-sensitive lipase (LIPE) enzymes, respectively. Regulates insulin-signaling and glycolysis by phosphorylating IRS1, PFKFB2 and PFKFB3. AMPK stimulates glucose uptake in muscle by increasing the translocation of the glucose transporter SLC2A4/GLUT4 to the plasma membrane, possibly by mediating phosphorylation of TBC1D4/AS160. Regulates transcription and chromatin structure by phosphorylating transcription regulators involved in energy metabolism such as CRTC2/TORC2, FOXO3, histone H2B, HDAC5, MEF2C, MLXIPL/ChREBP, EP300, HNF4A, p53/TP53, SREBF1, SREBF2 and PPARGC1A. Acts as a key regulator of glucose homeostasis in liver by phosphorylating CRTC2/TORC2, leading to CRTC2/TORC2 sequestration in the cytoplasm. In response to stress, phosphorylates 'Ser-36' of histone H2B (H2BS36ph), leading to promote transcription. Acts as a key regulator of cell growth and proliferation by phosphorylating TSC2, RPTOR and ATG1/ULK1: in response to nutrient limitation, negatively regulates the mTORC1 complex by phosphorylating RPTOR component of the mTORC1 complex and by phosphorylating and activating TSC2. In response to nutrient limitation, promotes autophagy by phosphorylating and activating ATG1/ULK1. AMPK also acts as a regulator of circadian rhythm by mediating phosphorylation of CRY1, leading to destabilize it. May regulate the Wnt signaling pathway by phosphorylating CTNNB1, leading to stabilize it. Also has tau-protein kinase activity: in response to amyloid beta A4 protein (APP) exposure, activated by CAMKK2, leading to phosphorylation of MAPT/TAU; however the relevance of such data remains unclear in vivo. Also phosphorylates CFTR, EEF2K, KLC1, NOS3 and SLC12A1.<ref>PMID:11518699</ref> <ref>PMID:11554766</ref> <ref>PMID:12519745</ref> <ref>PMID:14651849</ref> <ref>PMID:15866171</ref> <ref>PMID:17486097</ref> <ref>PMID:17711846</ref> <ref>PMID:18184930</ref> <ref>PMID:18439900</ref> <ref>PMID:20074060</ref> <ref>PMID:20160076</ref> <ref>PMID:21205641</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
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	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
	[[Category: ~~Human~~]]		[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
	[[Category: Gu, X]]		[[Category: Gu X]]
	[[Category: Ke, J]]		[[Category: Ke J]]
	[[Category: Li, X]]		[[Category: Li X]]
	[[Category: Melcher, K]]		[[Category: Melcher K]]
	[[Category: Tan~~, M H.E]]~~		[[Category: Tan MHE]]
	~~[[Category: Waal, P W.de~~]]		[[Category: Wang D]]
	[[Category: Wang, D]]		[[Category: Wang L]]
	[[Category: Wang, L]]		[[Category: Wu D]]
	[[Category: Wu, D]]		[[Category: Xu HE]]
	[[Category: Xu~~, H E~~]]		[[Category: Zhou XE]]
	[[Category: Zhou~~, X E~~]]		[[Category: De Waal PW]]
	[[Category: ~~Axin]]~~
	~~[[Category: Camkkbeta]]~~
	~~[[Category: Glycogen]]~~
	~~[[Category: Human alpha1 beta2 gamma1 holo-ampk complex]]~~
	~~[[Category: Lkb1]]~~
	~~[[Category: Phosphorylation]]~~
	~~[[Category: Serine/threonine protein kinase]]~~
	~~[[Category: Transferase~~]]

OCA at 10:18, 1 May 2019

2019-05-01T10:18:17Z

← Older revision		Revision as of 10:18, 1 May 2019
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	==Crystal structure of the phosphorylated human alpha1 beta2 gamma1 holo-AMPK complex bound to AMP and cyclodextrin==		==Crystal structure of the phosphorylated human alpha1 beta2 gamma1 holo-AMPK complex bound to AMP and cyclodextrin==
	<StructureSection load='4rer' size='340' side='right' caption='[[4rer]], [[Resolution\|resolution]] 4.05Å' scene=''>		<StructureSection load='4rer' size='340' side='right'caption='[[4rer]], [[Resolution\|resolution]] 4.05Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4rer]] is a 3 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4RER OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4RER FirstGlance]. <br>		<table><tr><td colspan='2'>[[4rer]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4RER OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4RER FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=AMP:ADENOSINE+MONOPHOSPHATE'>AMP</scene>, <scene name='pdbligand=BCD:BETA-CYCLODEXTRIN'>BCD</scene>, <scene name='pdbligand=EPE:4-(2-HYDROXYETHYL)-1-PIPERAZINE+ETHANESULFONIC+ACID'>EPE</scene>, <scene name='pdbligand=STU:STAUROSPORINE'>STU</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=AMP:ADENOSINE+MONOPHOSPHATE'>AMP</scene>, <scene name='pdbligand=BCD:BETA-CYCLODEXTRIN'>BCD</scene>, <scene name='pdbligand=EPE:4-(2-HYDROXYETHYL)-1-PIPERAZINE+ETHANESULFONIC+ACID'>EPE</scene>, <scene name='pdbligand=STU:STAUROSPORINE'>STU</scene></td></tr>
	<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=SEP:PHOSPHOSERINE'>SEP</scene>, <scene name='pdbligand=TPO:PHOSPHOTHREONINE'>TPO</scene></td></tr>		<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=SEP:PHOSPHOSERINE'>SEP</scene>, <scene name='pdbligand=TPO:PHOSPHOTHREONINE'>TPO</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4red\|4red]], [[4rew\|4rew]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4red\|4red]], [[4rew\|4rew]]</td></tr>
			<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">AMPK1, Human holo-AMPK alpha1 subunit, PRKAA1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), Human holo-AMPK beta2 subunit, PRKAB2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), Human holo-AMPK gamma1 subunit, PRKAG1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4rer FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4rer OCA], [http://pdbe.org/4rer PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4rer RCSB], [http://www.ebi.ac.uk/pdbsum/4rer PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4rer ProSAT]</span></td></tr>		<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4rer FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4rer OCA], [http://pdbe.org/4rer PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4rer RCSB], [http://www.ebi.ac.uk/pdbsum/4rer PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4rer ProSAT]</span></td></tr>
	</table>		</table>
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	==See Also==		==See Also==
	*[[AMP-activated protein kinase\|AMP-activated protein kinase]]		*[[AMP-activated protein kinase\|AMP-activated protein kinase]]
			*[[AMP-activated protein kinase 3D structures\|AMP-activated protein kinase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
			[[Category: Human]]
			[[Category: Large Structures]]
	[[Category: Gu, X]]		[[Category: Gu, X]]
	[[Category: Ke, J]]		[[Category: Ke, J]]

OCA at 17:21, 18 January 2017

2017-01-18T17:21:26Z

← Older revision		Revision as of 17:21, 18 January 2017
Line 1:		Line 1:

	==Crystal structure of the phosphorylated human alpha1 beta2 gamma1 holo-AMPK complex bound to AMP and cyclodextrin==		==Crystal structure of the phosphorylated human alpha1 beta2 gamma1 holo-AMPK complex bound to AMP and cyclodextrin==
	<StructureSection load='4rer' size='340' side='right' caption='[[4rer]], [[Resolution\|resolution]] 4.05Å' scene=''>		<StructureSection load='4rer' size='340' side='right' caption='[[4rer]], [[Resolution\|resolution]] 4.05Å' scene=''>
Line 6:		Line 7:
	<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=SEP:PHOSPHOSERINE'>SEP</scene>, <scene name='pdbligand=TPO:PHOSPHOTHREONINE'>TPO</scene></td></tr>		<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=SEP:PHOSPHOSERINE'>SEP</scene>, <scene name='pdbligand=TPO:PHOSPHOTHREONINE'>TPO</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4red\|4red]], [[4rew\|4rew]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4red\|4red]], [[4rew\|4rew]]</td></tr>
	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4rer FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4rer OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4rer RCSB], [http://www.ebi.ac.uk/pdbsum/4rer PDBsum]</span></td></tr>		<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4rer FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4rer OCA], [http://pdbe.org/4rer PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4rer RCSB], [http://www.ebi.ac.uk/pdbsum/4rer PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4rer ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 18:		Line 19:
	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>		From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
	</div>		</div>
			<div class="pdbe-citations 4rer" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==

OCA at 05:51, 11 March 2015

2015-03-11T05:51:55Z

← Older revision		Revision as of 05:51, 11 March 2015
Line 18:		Line 18:
	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>		From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
	</div>		</div>

			==See Also==
			*[[AMP-activated protein kinase\|AMP-activated protein kinase]]
	== References ==		== References ==
	<references/>		<references/>
Line 27:		Line 30:
	[[Category: Melcher, K]]		[[Category: Melcher, K]]
	[[Category: Tan, M H.E]]		[[Category: Tan, M H.E]]
	[[Category: Waal, P De]]		[[Category: Waal, P W.de]]
	[[Category: Wang, D]]		[[Category: Wang, D]]
	[[Category: Wang, L]]		[[Category: Wang, L]]

OCA at 02:59, 25 December 2014

2014-12-25T02:59:58Z

← Older revision		Revision as of 02:59, 25 December 2014
Line 8:		Line 8:
	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4rer FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4rer OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4rer RCSB], [http://www.ebi.ac.uk/pdbsum/4rer PDBsum]</span></td></tr>		<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4rer FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4rer OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4rer RCSB], [http://www.ebi.ac.uk/pdbsum/4rer PDBsum]</span></td></tr>
	</table>		</table>
			== Function ==
			[[http://www.uniprot.org/uniprot/AAPK1_HUMAN AAPK1_HUMAN]] Catalytic subunit of AMP-activated protein kinase (AMPK), an energy sensor protein kinase that plays a key role in regulating cellular energy metabolism. In response to reduction of intracellular ATP levels, AMPK activates energy-producing pathways and inhibits energy-consuming processes: inhibits protein, carbohydrate and lipid biosynthesis, as well as cell growth and proliferation. AMPK acts via direct phosphorylation of metabolic enzymes, and by longer-term effects via phosphorylation of transcription regulators. Also acts as a regulator of cellular polarity by remodeling the actin cytoskeleton; probably by indirectly activating myosin. Regulates lipid synthesis by phosphorylating and inactivating lipid metabolic enzymes such as ACACA, ACACB, GYS1, HMGCR and LIPE; regulates fatty acid and cholesterol synthesis by phosphorylating acetyl-CoA carboxylase (ACACA and ACACB) and hormone-sensitive lipase (LIPE) enzymes, respectively. Regulates insulin-signaling and glycolysis by phosphorylating IRS1, PFKFB2 and PFKFB3. AMPK stimulates glucose uptake in muscle by increasing the translocation of the glucose transporter SLC2A4/GLUT4 to the plasma membrane, possibly by mediating phosphorylation of TBC1D4/AS160. Regulates transcription and chromatin structure by phosphorylating transcription regulators involved in energy metabolism such as CRTC2/TORC2, FOXO3, histone H2B, HDAC5, MEF2C, MLXIPL/ChREBP, EP300, HNF4A, p53/TP53, SREBF1, SREBF2 and PPARGC1A. Acts as a key regulator of glucose homeostasis in liver by phosphorylating CRTC2/TORC2, leading to CRTC2/TORC2 sequestration in the cytoplasm. In response to stress, phosphorylates 'Ser-36' of histone H2B (H2BS36ph), leading to promote transcription. Acts as a key regulator of cell growth and proliferation by phosphorylating TSC2, RPTOR and ATG1/ULK1: in response to nutrient limitation, negatively regulates the mTORC1 complex by phosphorylating RPTOR component of the mTORC1 complex and by phosphorylating and activating TSC2. In response to nutrient limitation, promotes autophagy by phosphorylating and activating ATG1/ULK1. AMPK also acts as a regulator of circadian rhythm by mediating phosphorylation of CRY1, leading to destabilize it. May regulate the Wnt signaling pathway by phosphorylating CTNNB1, leading to stabilize it. Also has tau-protein kinase activity: in response to amyloid beta A4 protein (APP) exposure, activated by CAMKK2, leading to phosphorylation of MAPT/TAU; however the relevance of such data remains unclear in vivo. Also phosphorylates CFTR, EEF2K, KLC1, NOS3 and SLC12A1.<ref>PMID:11518699</ref> <ref>PMID:11554766</ref> <ref>PMID:12519745</ref> <ref>PMID:14651849</ref> <ref>PMID:15866171</ref> <ref>PMID:17486097</ref> <ref>PMID:17711846</ref> <ref>PMID:18184930</ref> <ref>PMID:18439900</ref> <ref>PMID:20074060</ref> <ref>PMID:20160076</ref> <ref>PMID:21205641</ref> [[http://www.uniprot.org/uniprot/AAKG1_HUMAN AAKG1_HUMAN]] AMP/ATP-binding subunit of AMP-activated protein kinase (AMPK), an energy sensor protein kinase that plays a key role in regulating cellular energy metabolism. In response to reduction of intracellular ATP levels, AMPK activates energy-producing pathways and inhibits energy-consuming processes: inhibits protein, carbohydrate and lipid biosynthesis, as well as cell growth and proliferation. AMPK acts via direct phosphorylation of metabolic enzymes, and by longer-term effects via phosphorylation of transcription regulators. Also acts as a regulator of cellular polarity by remodeling the actin cytoskeleton; probably by indirectly activating myosin. Gamma non-catalytic subunit mediates binding to AMP, ADP and ATP, leading to activate or inhibit AMPK: AMP-binding results in allosteric activation of alpha catalytic subunit (PRKAA1 or PRKAA2) both by inducing phosphorylation and preventing dephosphorylation of catalytic subunits. ADP also stimulates phosphorylation, without stimulating already phosphorylated catalytic subunit. ATP promotes dephosphorylation of catalytic subunit, rendering the AMPK enzyme inactive.<ref>PMID:21680840</ref> [[http://www.uniprot.org/uniprot/AAKB2_HUMAN AAKB2_HUMAN]] Non-catalytic subunit of AMP-activated protein kinase (AMPK), an energy sensor protein kinase that plays a key role in regulating cellular energy metabolism. In response to reduction of intracellular ATP levels, AMPK activates energy-producing pathways and inhibits energy-consuming processes: inhibits protein, carbohydrate and lipid biosynthesis, as well as cell growth and proliferation. AMPK acts via direct phosphorylation of metabolic enzymes, and by longer-term effects via phosphorylation of transcription regulators. Also acts as a regulator of cellular polarity by remodeling the actin cytoskeleton; probably by indirectly activating myosin. Beta non-catalytic subunit acts as a scaffold on which the AMPK complex assembles, via its C-terminus that bridges alpha (PRKAA1 or PRKAA2) and gamma subunits (PRKAG1, PRKAG2 or PRKAG3).
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==

OCA at 16:04, 10 December 2014

2014-12-10T16:04:31Z

@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
+==Crystal structure of the phosphorylated human alpha1 beta2 gamma1 holo-AMPK complex bound to AMP and cyclodextrin==
-The entry 4rer is ON HOLD
+Structural basis of AMPK regulation by adenine nucleotides and glycogen.,Li X, Wang L, Zhou XE, Ke J, de Waal PW, Gu X, Tan MH, Wang D, Wu D, Xu HE, Melcher K Cell Res. 2014 Nov 21. doi: 10.1038/cr.2014.150. PMID:25412657<ref>PMID:25412657</ref>
-Authors: Zhou, X.E., Ke, J., Li, X., Wang, L., Gu, X., De Waal, P., Tan, M.H.E., Wang, D., Wu, D., Xu, H.E., Melcher, K.
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
-Description: Crystal structure of the phosphorylated human alpha1 beta2 gamma1 holo-AMPK complex bound to AMP and cyclodextrin
+== References ==

OCA: Protected "4rer" [edit=sysop:move=sysop]

2014-10-01T23:11:40Z

Protected "4rer" [edit=sysop:move=sysop]

← Older revision	Revision as of 23:11, 1 October 2014
(No difference)

OCA: New page: '''Unreleased structure''' The entry 4rer is ON HOLD Authors: Zhou, X.E., Ke, J., Li, X., Wang, L., Gu, X., De Waal, P., Tan, M.H.E., Wang, D., Wu, D., Xu, H.E., Melcher, K. Descriptio...

2014-10-01T23:11:39Z

New page: '''Unreleased structure''' The entry 4rer is ON HOLD Authors: Zhou, X.E., Ke, J., Li, X., Wang, L., Gu, X., De Waal, P., Tan, M.H.E., Wang, D., Wu, D., Xu, H.E., Melcher, K. Descriptio...

New page

'''Unreleased structure'''

The entry 4rer is ON HOLD

Authors: Zhou, X.E., Ke, J., Li, X., Wang, L., Gu, X., De Waal, P., Tan, M.H.E., Wang, D., Wu, D., Xu, H.E., Melcher, K.

Description: Crystal structure of the phosphorylated human alpha1 beta2 gamma1 holo-AMPK complex bound to AMP and cyclodextrin